Table 1 ACMG’s proposed approach to risk classification and oversight of laboratory-developed tests for inherited conditions.

Low risk

The consequence of an incorrect result is unlikely to lead to serious morbidity or mortality for patients or their blood relatives. The test result is typically used in conjunction with other clinical findings to establish or confirm a diagnosis; no claim that the test result alone determines prognosis or direction of therapy.

AND

All aspects of the test methodology are well-established, commonly performed, and commonly applied to the clinical indication.

The laboratory internally performs analytical validation and determines adequacy of clinical validation before offering for clinical testing; the accreditor will verify that the laboratory performed appropriate validation studies during routinely scheduled inspections.

The lab is overseen, and the test is developed and validated by a board-certified MD (ABPath/ABMGG), PhD (ABMGG), or equivalently trained and certified professional.

N/A

Moderate risk

The consequence of an incorrect result may lead to serious morbidity or mortality for patients or their blood relatives. The test result may be used for predicting disease progression or identifying whether a patient is eligible for a specific therapy.

AND

Test methodology is well understood and independently verifiable; interlaboratory comparisons can be performed or external proficiency testing is available.

The laboratory internally performs analytical validation and determines adequacy of clinical validation. Laboratory notifies third-party accreditor and provides validation summary prior to offering for clinical testing. Third-party review and approval not required prior to launch. Accreditor has option to request additional documents for review and/or may delay or suspend clinical testing.

The lab is overseen, the test is developed and validated, and the test results are interpreted by a board-certified MD (ABPath/ABMGG), PhD (ABMGG), or equivalently trained and certified professional.

N/A

High risk

The consequence of an incorrect result could lead to serious morbidity or mortality for patients or their blood relatives. The test is used to predict risk of a disease associated with, progression of a disease associated with, or patient eligibility for a specific therapy associated with significant morbidity or mortality.

AND

Test methodology is based on a unique algorithm or proprietary method and result is not independently verifiable (interlaboratory comparisons cannot be performed).

The laboratory must submit comprehensive validation documentation to the third-party accreditor for review and receive approval before offering the test clinically. The accreditor determines compliance. Because of constantly expanding knowledge and technology, a rapid turnaround time for the accreditor review is necessary.

The lab is overseen, the test is developed and validated, and the test results are interpreted by a board-certified MD (ABPath/ABMGG), PhD (ABMGG), or equivalently trained and certified professional.

External, regulated proficiency testing is available in which the lab actively participates.

Established clinical protocol for use of test, including provider and patient education components. May include user comprehension verification.

Extensive peer-reviewed literature establishing the analytical parameters and clinical utility of the test.

Appropriate labeling, advertising, and information on laboratory website and provided when requested.